The present relates to systems and methods for the UV-irradiation of a biological fluid for the purposes of reduction of pathogens therein. While the primary object of the invention is to treat blood, blood-based products and synthetic blood substitutes, the concepts of the present invention may be used for treating other fluids such as those encountered in beverage industries including dairy, distilling and brewing, as well as in water treatment industries including sewerage and purification systems. Other uses of the invention contemplate treating blood from a subject and returning the blood to the subject after completion of the treatment.
The term “pathogens” is used broadly for the purposes of the present invention to include a variety of harmful microorganisms such as bacteria, fungi, viruses (including among others a human immunodeficiency virus, a hepatitis A, B and C virus, an influenza virus, a hemorrhagic fever virus such as Ebola virus etc.), parasites, molds, yeasts and other similar organisms which may be found in human or non-human blood and products derived from blood, as well as various other body fluids such (as for example milk) and synthetic fluids manufactured for use as replacements for any such body fluids or components thereof.
Blood transfusion in developed countries is very safe with regard to avoidance of transmitting of an infectious disease. This is primarily achieved by donor exclusion using questionnaires and screening for pathogens presence by means of serological methods and direct testing for nucleic acids. Despite these practices, there remains a risk of transmission of pathogens with the transfusion of cellular components of blood (such as red cells and platelets for example). This is at least in part because current screening tests leave a window of time after infection and before their sensitivity allows for detection of pathogens. In addition, screening does not takes place for rarely occurring pathogens or as yet unknown transmissible pathogens (Soland, E. M. et al. J. Am. Med. Assoc. 274: 1368-1373 (1995); Schreiber, G. B. et al. New Engl. J. Med. 334: 1685-1690 (1996); Valinsky, J. E. In: Blood Safety and Surveillance, Linden, J. V. and Bianco, C., Eds., Marcel Dekker, N Y, 2001, pp. 185-219).
The use of pathogen reduction technologies has the potential of eliminating the remaining risks of transmission of infectious disease as a result of blood transfusion. Various approaches have been used to sterilize blood components (Ben-Hur, E. and B. Horowitz AIDS 10: 1183-1190 (1996); Ben-Hur, E. and R. P. Goodrich, In: Photodynamic Inactivation of Microbial Pathogens, Hamblin, M. R. and J. Gori, Eds. RSC Publishing, UK, 2011, pp. 233-263). The most promising methods are photochemical ones, two of which were approved by regulatory agencies for pathogen reduction in platelet concentrates. The Intercept method employs a psoralen and UVA light (Lin, L. et al. Transfusion 37: 423-435 (1997)) and the Mirasol method uses riboflavin and UVA+UVB light (Goodrich, R. P. et al. Transfusion Apheresis Sci. 35: 5-17 (2006)).
Short wavelengths ultraviolet light (UVC, 180-290 nm) is a known sterilizing agent that targets the nucleic acids of microorganisms (Setlow, R. B. and J. K. Setlow Proc. Natl. Acad. USA 48: 1250-1253 (1962)). It has been used for pathogen reduction in optically-transparent biological fluids such as plasma (Chin, S. et al. Blood 86: 4331-4336 (1995)) and is being studied also in platelet concentrates (Bashir, S. et al. Transfusion 53: 990-1000 (2013)). However, in opaque biological fluids such as red cell concentrates as well as in whole blood, UVC penetration is very limited due to absorption of UV irradiation by the red cells. As a result, all attempts to use UV irradiation for sterilizing whole blood or red cells have been unsuccessful so far.
Therefore, there is a need for an effective system and method for reducing pathogens in a biological fluid such as blood.
Attempts to irradiate blood or other opaque biological fluids with UV light have been described before. The exposure of a biological fluid to UV irradiation can result in damage to various components of the biological fluid, for example enzymes and other functional proteins. Therefore, the UV irradiation source should not be too powerful nor may the fluid be exposed to the UV radiation for too long, if one is to avoid damaging the components of the biological fluid. On the other hand, sufficient UVC energy needs to be transmitted to the blood flow to assure substantial reduction and effective elimination of the pathogens. This balance is critical in achieving desired effectiveness of UVC treatment.
To ensure that substantially all of the fluid receives a sufficient dose of UV radiation, it has been found that intensive mixing of the fluid to be treated during UV irradiation increases the efficiency of the irradiation process. A variety of devices that include static mixers placed in the fluid flow pathway have been proposed such as those described in U.S. Pat. Nos. 6,312,593; 7,175,808; US Pat. Application Publications 2004/0039325; 2006/0270960; or PCT publications WO1997046271; WO2000020045.
In addition to mixing, a sufficient intensity of the UV irradiation needs to be provided by a source of UV irradiation. Traditional devices used as such source include low pressure and medium pressure mercury UV lamps, amalgam UV lamps, arc UV lamps, fluorescent UV lamps, halogen UV lamps, and xenon UV lamps. Such lamps have a number of disadvantages when used directly for the purposes of the present invention as they produce low level of UV output given the energy requirements, have large size, fragile and if broken represent an environmental hazard of mercury contamination. In addition, traditional UV lamps produce UV output over a broad range of UV wavelengths, some of which may be harmful to the biological fluid.
There is a need for a new exposure chamber and a new system for reducing pathogens in a biological fluid with improved source of UV irradiation and specifically with the ability to provide high intensity of UV light in a small physical size. There is also a need for a new source of UV irradiation to provide efficacious UV irradiation at desired peak wavelength with low energy consumption.